The ABC transporter MsbA adopts the wide inward-open conformation in E. coli cells

Autor(en): Galazzo, Laura
Meier, Gianmarco
Januliene, Dovile 
Parey, Kristian 
De Vecchis, Dario
Striednig, Bianca
Hilbi, Hubert
Schaefer, V, Lars
Kuprov, Ilya
Moeller, Arne 
Bordignon, Enrica
Seeger, Markus A.
Stichwörter: ATP-BINDING; BINDING CASSETTE TRANSPORTER; CRYO-EM; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; FLEXIBILITY; MOLECULAR-DYNAMICS; Multidisciplinary Sciences; NANOBODIES; P-GLYCOPROTEIN REVEAL; Science & Technology - Other Topics; STRUCTURAL BASIS
Erscheinungsdatum: 2022
Herausgeber: AMER ASSOC ADVANCEMENT SCIENCE
Journal: SCIENCE ADVANCES
Volumen: 8
Ausgabe: 41
Zusammenfassung: 
Membrane proteins are currently investigated after detergent extraction from native cellular membranes and reconstitution into artificial liposomes or nanodiscs, thereby removing them from their physiological environment. However, to truly understand the biophysical properties of membrane proteins in a physiological environment, they must be investigated within living cells. Here, we used a spin-labeled nanobody to interrogate the conformational cycle of the ABC transporter MsbA by double electron-electron resonance. Unexpectedly, the wide inward-open conformation of MsbA, commonly considered a nonphysiological state, was found to be prominently populated in Escherichia coli cells. Molecular dynamics simulations revealed that extensive lateral portal opening is essential to provide access of its large natural substrate core lipid A to the binding cavity. Our work paves the way to investigate the conformational landscape of membrane proteins in cells.
ISSN: 2375-2548
DOI: 10.1126/sciadv.abn6845

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